BLOSSOM trial of lorcaserin demonstrates
improvements in patients' body composition, cardiovascular risk factors and quality
of life
Data from the BLOSSOM (Behavioral modification and LOrcaserin
Second Study for Obesity Management) Phase 3 trial demonstrates improvements in
patients' body composition, cardiovascular risk factors and quality of life. These
findings add to the previously announced top-line BLOSSOM data that showed highly
significant weight loss with lorcaserin over one year of treatment in 4,008 patients.
The late-breaking data were presented by Lee Kaplan,
M.D., Ph.D., Associate Professor of Medicine at Harvard Medical School and Director
of the Massachusetts General Hospital Weight Center, at Obesity 2009, the 27th
Annual Scientific Meeting of The Obesity Society.
"Safety is of paramount importance in treating patients
who are overweight or have obesity," said Dr. Kaplan. "We need new therapies
that help patients reduce their weight and improve cardiovascular factors such
as high blood pressure and cholesterol, while avoiding cardiac toxicity and symptoms
of depression. Lorcaserin works by selectively affecting a unique and important
pathway, which allows for significant weight loss and improvements in these important
risk factors, along with an excellent safety and tolerability profile."
William R. Shanahan, M.D., Arena's Vice President and
Chief Medical Officer, stated, "Treatment with lorcaserin offers patients
the opportunity to achieve sustainable weight loss in a well-tolerated manner,
resulting in improved cardiometabolic health and quality of life. In order to
improve overall health, it's important to see these measurements moving in the
right direction as patients reduce their weight. Based on lorcaserin's safety
and efficacy profile, we expect primary care physicians to find lorcaserin an
attractive first-line therapy for weight management."
Specifically, the new data demonstrate that treatment
with lorcaserin over one year was associated with highly significant improvements
or favorable trends compared to placebo in multiple secondary endpoints evaluated
in the trial.
Using Intent-to-Treat Last Observation Carried Forward
(ITT-LOCF) analysis, lorcaserin patients achieved highly significant improvements
in Body Mass Index (BMI), waist circumference and hip circumference. Changes from
baseline for patients who took lorcaserin twice daily, lorcaserin once daily or
placebo, respectively, were as follows: BMI (kg/m squared), (-2.1, -1.7, -1.0);
waist circumference (cm), (-6.2, -5.6, -4.2); and hip circumference (cm), (-5.3,
-5.0, -3.3), (p<0.0001) compared to placebo for all measurements. In addition,
lorcaserin patients lost significantly more body fat than the placebo patients.
Using ITT-LOCF analysis, lorcaserin helped improve patients'
cardiovascular risk factors. Patients dosed with 10 mg of lorcaserin once or twice
daily achieved statistical significance (p<0.05) versus placebo at Week 52
for percent change in HDL cholesterol and triglycerides and achieved favorable
trends in total cholesterol and LDL cholesterol. Lorcaserin did not increase blood
pressure or heart rate at any time point. Changes from baseline for patients who
took lorcaserin twice daily, lorcaserin once daily or placebo, respectively, were
as follows: diastolic blood pressure (mmHg), (-1.9, -1.0, -1.9); systolic blood
pressure (mmHg), (-2.0, -1.1, -1.2); and heart rate (bpm), (-2.3, -1.1, -1.6).
Lorcaserin did not increase depression or suicidal ideation
compared to placebo. Adverse events related to depression and their rates for
patients who took lorcaserin twice daily, lorcaserin once daily or placebo, respectively,
were as follows: depression (1.9%, 1.1%, 1.8%); depressed mood (0.6%, 0.9%, 0.9%);
and depressive symptoms (<0.1%, 0%, 0%).
Quality of Life, as assessed by the Impact of Weight
on Quality of Life-Lite (IWQOL-Lite) questionnaire, improved to a significantly
greater extent in the lorcaserin twice daily (p<0.0001) and lorcaserin once
daily (p<0.01) groups as compared to placebo at Week 52. All measurements,
including physical function, self-esteem, sexual life, public distress and work,
improved in a dose-dependent fashion.
Lorcaserin was very well tolerated. Adverse events that
exceeded placebo by greater than 3% and their rates for patients who took lorcaserin
twice daily, lorcaserin once daily or placebo, respectively, were as follows:
headache (15.6%, 15.6%, 9.2%); nausea (9.1%, 7.6%, 5.3%); dizziness (8.7%, 6.2%,
3.9%); fatigue (8.4%, 6.6%, 4.1%); and dry mouth ( 5.4%, 3.4%, 2.3%). Serious
adverse events occurred infrequently and their rates for patients who took lorcaserin
twice daily, lorcaserin once daily or placebo, respectively, were as follows:
3.1%, 3.4% and 2.2%.
The assessment of echocardiograms performed at baseline
and after patients completed 6 and 12 months of dosing indicated that lorcaserin
did not increase echocardiographic heart valve regurgitation. Lorcaserin met the
primary safety endpoint that evaluated the rates of new FDA-defined valvulopathy
in BLOSSOM at Week 52: lorcaserin 10 mg twice daily (2.0%), 10 mg once daily (1.4%)
and placebo (2.0%). The integrated BLOOM (Behavioral modification and Lorcaserin
for Overweight and Obesity Management) and BLOSSOM echocardiography data set rules
out a risk of valvulopathy in lorcaserin patients according to criteria requested
by the FDA.
New data demonstrate that similar numbers of mitral insufficiency
and aortic insufficiency shifts were reported for patients on lorcaserin and placebo.
In patients with pre-existing FDA-defined valvulopathy at baseline, changes in
valvular regurgitant scores did not differ between the placebo and lorcaserin
groups. The majority of patients experienced either no change or an improvement
in valvular regurgitation.
The previously announced BLOSSOM data demonstrated that
lorcaserin was highly efficacious, achieving statistical significance on all three
co-primary efficacy endpoints, and was very well tolerated. Lorcaserin patients
achieved highly significant categorical and absolute weight loss over 52 weeks
of treatment. About two-thirds (63.2%) of lorcaserin patients dosed twice daily
who completed the trial according to the protocol lost at least 5% of their weight,
compared to 34.9% of patients on placebo, and more than one-third (35.1%) of these
lorcaserin patients lost at least 10% of their weight, compared to 16.1% for placebo.
The average weight loss for lorcaserin patients dosed twice daily was 17.0 pounds,
compared to 8.7 pounds for placebo. The top quartile of lorcaserin patients who
completed the trial according to protocol and had their Week 52 weight recorded
lost an average of 35.1 pounds.
BLOSSOM evaluated 4,008 patients with an average BMI
of 35.9 and baseline weight of 220 pounds. The Week 52 completion rate was higher
for patients on lorcaserin 10 mg twice daily (57.2%) and 10 mg once daily (59.0%)
compared to patients on placebo (52.0%). Discontinuations for adverse events were
low and as follows: lorcaserin 10 mg twice daily (7.2%), 10 mg once daily (6.2%)
and placebo (4.6%).
BLOSSOM is a double blind, randomized, placebo-controlled
trial in approximately 100 sites in the US. The trial evaluated 10 mg of lorcaserin
dosed once or twice daily versus placebo over a one-year treatment period in obese
patients (BMI 30 to 45) with or without co-morbid conditions and overweight patients
(BMI 27 to less than 30) with at least one co-morbid condition. Patients were
randomized at baseline in a 2:2:1 ratio to lorcaserin 10 mg twice daily, placebo
or lorcaserin 10 mg once daily. Patients received echocardiograms at baseline,
month 6 and at the end of the trial to assess heart valve function over time.
In contrast to the BLOOM trial, there were no echocardiographic exclusion criteria
for entry into BLOSSOM and there was no oversight or interim data review monitoring
by an independent safety monitoring board.
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